What type of variants typically cause CFTR-related pancreatitis?

Biallelic pathogenic variants are responsible for causing CFTR-related pancreatitis because they result in a significant disruption of the CFTR gene's function. The CFTR gene encodes the cystic fibrosis transmembrane conductance regulator, which functions as a chloride channel in epithelial cells. Pathogenic variants, particularly when present in both alleles (biallelic), can lead to the dysfunction of this protein. This dysfunction impacts fluid and electrolyte transport in the pancreas, ultimately causing the pancreatitis typically observed in patients with cystic fibrosis or CFTR-related disorders.

Inadequate function of CFTR can lead to thickened secretions and obstructions in the pancreatic ducts, which are crucial for the proper drainage of digestive enzymes. This obstruction promotes inflammation and damage to pancreatic tissue, resulting in pancreatitis.

While single nucleotide polymorphisms can affect CFTR function, they are typically not sufficient on their own to cause the disease. Chromosomal rearrangements and deletions in chromosome 7 may also impact the CFTR gene but are less commonly implicated in CFTR-related pancreatitis when compared to biallelic pathogenic variants, which have a direct role in manifesting the clinical symptoms associated with this condition. Thus, the clear connection between bialle